Breast Milk’s RSV Defense Unveiled in New Study

In a recent review published in the journal Advances in Nutrition, researchers delved into the existing evidence regarding the role of human milk oligosaccharides (HMOs) in safeguarding infants against respiratory syncytial virus – RSV infection and disease, emphasizing potential mechanisms and future avenues of research.

Background

RSV, a frequent cause of pediatric respiratory ailments, notably affects infants under two years old, leading to substantial morbidity and mortality. Apart from immediate health consequences, RSV infection could impact long-term immune development and overall health outcomes.

The substantial disease burden of RSV infection in infants, combined with the lack of effective treatments, underscores the urgent necessity for prophylactic strategies. Breastfeeding has demonstrated consistent protection against severe RSV disease, possibly attributable to the bioactive constituents in breast milk, including HMOs. Recent studies have linked HMOs to decreased risk of lower respiratory infections and reduced viral load and inflammation in infants, highlighting their potential role in RSV infection prevention and management.

Overview of human milk oligosaccharides HMOs, abundant in human milk, play diverse roles in infant development. They are synthesized from lactose and can form various structures with additional sugars like GlcNAc, Gal, Fuc, and Neu5Ac. The concentration and composition of HMOs vary among individuals and populations due to genetic and environmental factors. HMOs resist digestion and reach the colon intact, where they modulate the microbiome, inhibit pathogen binding, reduce inflammation, and modulate the immune system, potentially contributing to viral infection prevention in breastfed infants.

HMOs mitigate respiratory infection risk Clinical studies have explored the connection between HMOs and respiratory symptoms in infants, particularly focusing on their potential preventive effects against RSV infection and other respiratory diseases. Lower levels of lacto-N-fucopentaose II (LNFP-II) in maternal milk and infant feces were associated with increased respiratory symptoms in infants. Another study demonstrated that infant formula containing 2’-fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT) reduced the incidence of lower respiratory tract infections and bronchitis in infants. Additionally, the maternal secretor genotype, influencing the production of α1-2 fucosylated HMOs, was associated with reduced acute respiratory infection risk in breastfed infants. However, certain studies did not find a significant association between HMOs and respiratory infections. Further research is needed to elucidate the precise mechanisms and effects of HMO consumption on RSV incidence and severity, considering factors such as HMO composition, secretor status, and microbiome composition.

HMOs exhibit antiviral activity

HMOs demonstrate antiviral properties by binding to clinically relevant viruses, including rotavirus, norovirus, human immunodeficiency virus (HIV), and influenza. For instance, α1-2 fucosylated HMOs like 2’-FL can occupy norovirus binding sites, reducing infectivity. Additionally, certain HMOs compete with HIV-1 for binding sites on dendritic cells, potentially reducing transmission. Despite human milk’s ability to transmit viruses, it rarely causes disease in infants, likely owing to the antiviral properties of HMOs. The structural diversity of HMOs provides a broad range of protection against viral infections, with implications for preventing diseases like coronavirus disease 2019 (COVID-19). However, research on HMOs’ ability to prevent RSV infection and pro-inflammatory responses remains limited compared to other viruses.

Modulating the host’s innate response Exposure to certain HMOs alters the response of human respiratory and peripheral blood mononuclear cells (PBMCs) to RSV infection. These HMOs reduce RSV viral load and cytokines linked to disease severity and inflammation in respiratory cells and PBMCs. Infants fed formula containing 2’-FL also exhibit lower plasma levels of inflammatory cytokines when challenged with RSV, similar to breastfed infants. Therefore, HMO supplementation may enhance resistance to RSV infection in infants, potentially explaining the reduced risk of severe RSV disease observed in breastfed infants.

Modulating gut microbiome to mitigate RSV disease severity

The gut-lung axis concept suggests that gut microbiota can influence immune defense against respiratory infections like RSV beyond the gastrointestinal tract. Changes in the gut microbiome and associated metabolites are linked to the incidence and severity of respiratory infections such as RSV. Research on infant formula indicates that 2’-FL and LNnT can promote a Bifidobacterium-dominated microbiota in some infants, potentially reducing the need for antibiotics. Additionally, elevated fecal fucosylated glycans, lactate, acetate, and Bifidobacterium are associated with reduced risk of bronchitis or lower respiratory tract infections in infants.

Acetate, produced by gut bacteria in response to specific HMOs, may enhance immune responses against RSV infection. Animal studies demonstrate that acetate supplementation can protect against RSV-induced lung inflammation, and clinical observations in infants with RSV bronchiolitis suggest that high levels of fecal acetate are associated with milder symptoms.

Conclusion and future perspectives

HMOs hold promise in combating RSV through multiple mechanisms, including direct antiviral action and gut microbiota modulation. Standardized methods for identifying HMOs are crucial. Future studies should optimize designs to investigate HMO effects on RSV. Extensive birth-cohort studies could provide valuable insights. Key questions include identifying specific protective HMOs against RSV and understanding their mechanisms of action.

For more information: Human milk oligosaccharides and respiratory syncytial virus infection in infants.  Advances in Nutrition, https://doi.org/10.1016/j.advnut.2024.100218